We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study, we report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in MRI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3−5 nm) gadolinium oxide (DEG-Gd₂O₃) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd₂O₃ nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd₂O₃ nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r₁ and r₂ values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd₂O₃. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is, an extremely high MR signal at the cellular and molecular level.

Chelated gadolinium ions, e. g., GdDTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4-5-nm-sized Gd2O3 nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r(1) and r(2) values almost as high as those for free Gd3+ ions in water. The Gd2O3 nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.

Sub 5 nm sized manganese oxide nanoparticles; MnOx (1 ≤ x ≤ 2), were synthesized via a short time room temperature synthesis route. The nanoparticles are crystalline, spherically shaped and in the size range of 2-4 nm as shown by transmission electron microscopy studies. Selected area electron diffraction patterns were collected and their appearance indicated that the nanoparticle cores are composed of MnO. Also, co-existence of the (II) and (III) oxidation states at the nanoparticle surface was verified by results achieved from infrared spectroscopy and X-ray photoelectron spectroscopy. These measurements also supported presence of a minor amount of acetate groups as well as a negligible fraction of carbonate groups at the nanoparticle surfaces. The interpretation of the IR spectra was confirmed by quantum chemical calculations using the high spin manganese nanoparticle Mn₁₂O₁₂(OAc)₁₆(H₂O)₄, as a model system for the MnO_x nanoparticle surface. Bulk MnO and Mn2O3 are known to be antiferromagnetic. The magnetic properties are however somewhat dependent of the crystallite size and changes when scaling down to the nanoregion. The MnO_x (1 ≤ x ≤ 2) nanoparticles investigated in this work show a superparamagnetic behavior with a blocking temperature of approximately 12 K proven by means of SQUID measurements. The relaxivities of the nanoparticles and the Mn(OAc)2 precursors were studied with a bench top NMR analyzer verifying nanoparticle r1 and r2 of 0.5 and 6 mMs^-1 respectively. The r1 relaxivity is lower than what is earlier reported for Gd based contrast agent, but improvements are expected by further surface modification, due to increased rotational time and higher water dispersability.

A method to prepare amyloid-like fibrils functionalized with magnetic nanoparticles has been developed. The amyloid-like fibrils are prepared in a two step procedure, where insulin and magnetic nanoparticles are mixed simply by grinding in the solid state, resulting in a water soluble hybrid material. When the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid material self assembles to form amyloid-like fibrils incorporating the magnetic nanoparticles. This results in magnetically labeled amyloid-like fibrils which has been characterized by Transmission Electron Microscopy (TEM) and electron tomography. The influence of the aggregation process on proton relaxivity is investigated. The prepared materials have potential uses in a range of bio-imaging applications.

Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle-protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both danger signals, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations.

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Electrochemical impedance spectroscopy was employed to explore the possibility of relating the permeation of electrolyte ions in ?-functionalized self-assembled monolayers to structural or polarity changes induced by interaction with metal ions. The monolayers were based on alkanethiols modified with a phosphorylated tyrosine analogue, which from previous work are known to drastically change their organization on gold surfaces upon interaction with aluminum and magnesium ions. The ion permeation was evaluated by using relatively low excitation frequencies, 1000 to 2 Hz, and quantified by an extra resistive component in the equivalent circuit (R SAM). The extent of ion permeation influenced by the dc potential, the electrolyte concentration, the functional group, and the thiol length were also investigated. It was, for example, found that RSAM decreased ~20% when the thiol organization collapsed and that RSAM increased ~4-5 times when the electrolyte concentration was decreased by 1 order of magnitude. Interesting observations were also made regarding the potential dependence of RSAM and the double layer capacitance. The evaluation of the ion permeation can be used to indirectly detect whether the organization of a SAM is influenced by, for example, electric fields or chemical and biological interactions. This analysis can be performed without addition of redox species, but is on the other hand complicated by the fact that other factors also influence the presence of ions within the monolayer. In addition, a second parallel RC process was obtained in some of the impedance spectra when using even lower frequencies, and its resistive component revealed different results compared to RSAM. Such data may be useful for the understanding of complex double layer phenomena at modified electrodes. © 2007 American Chemical Society.

A biomimetic model system based on long-chain alkanethiols tailored with serine, threonine and tyrosine side-chain groups is created as a platform for the study of phosphorylated amino acids. The phosphorylated analogues are synthesized with protective tert-butyl groups that after assembly on thin polycrystalline gold films are removed in an acidic deprotection solution to form the corresponding phosphate self-assembled monolayers (SAMs). The SAMs are thoroughly characterized with null ellipsometry, contact angle goniometry, infrared reflection–absorption spectroscopy and X-ray photoelectron spectroscopy. The assembly and the subsequent deprotection process are optimized with respect to molecular orientation and chain conformation by varying the incubation time and the exposure time to the deprotection solution. The high quality of the generated SAMs suggests that the present assembly/deprotection approach is an attractive alternative when traditional synthetic routes become demanding because of solubility problems.

Neutrophil granulocytes are the most abundant white blood cells in mammals and vital components of the immune system. They are involved in the early phase of inflammation and in generation of reactive oxygen species. These rapid cell-signaling communicative processes are performed in the time frame of minutes. In this work, the activity and the response of neutrophil granulocytes are monitored when triggered by cerium-oxide based nanoparticles, using capacitive sensors based on Lab-on-a-chip technology. The chip is designed to monitor activation processes of cells during nanoparticle exposure, which is for the first time recorded on-line as alteration of the capacitance. The complementary metal oxide semiconductor engineering chip design is combined with low temperature co-fired ceramic, LTCC, packaging technology. The method is label free and gently measures cells on top of an insulating surface in a weak electromagnetic field, as compared to commonly used four-point probes and impedance spectroscopy electric measurements where electrodes are in direct contact with the cells. In summary, this label free method is used to measure oxidative stress of neutrophil granulocytes in real time, minute by minute and visualize the difference in moderate and high cellular workload during exposure of external triggers. It clearly shows the capability of this method to detect cell response during exposure of external triggers. In this way, an informationally dense non-invasive method is obtained, to monitor cells at work.

Transition-metal oxides (TMOs) are potential candidates for anode materials of lithium-ion batteries (LIBs) due to their high theoretical capacity (similar to 1000 mA h/g) and enhanced safety from suppressing the formation of lithium dendrites. However, the poor electron conductivity and the large volume expansion during lithiation/delithiation processes are still the main hurdles for the practical usage of TMOs as anode materials. In this work, the CoSnO3@NC@ MnO@NC hierarchical nanobox (CNMN) is then proposed and fabricated to solve those issues. The as-prepared nanobox contains hollow cubic CoSnO3 as a core and dual N-doped carbon-"sandwiched" MnO particles as a shell. As anode materials of LIBs, the hollow and carbon interlayer structures effectively accommodate the volume expansion while dual active TMOs of CoSnO3 and Notably, the dual-layer structure of N-doped carbons plays a critical functional role MnO efficiently increase the specific capacity. in the incorporated composites, where the inner layer serves as a reaction substrate and a spatial barrier and the outer layer offers electron conductivity, enabling more effective involvement of active anode materials in lithium storage, as well as maintaining their high activity during lithium cycling. Subsequently, the as-prepared CNMN exhibits a high specific capacity of 1195 mA h/g after the 200th cycle at 0.1C and an excellent stable reversible capacity of about 876 mA h/g after the 300th cycle at 0.5C with only 0.07 mA h/g fade per cycle after 300 cycles. Even after a 250 times fast charging/discharging cycle both at SC, it still retains a reversible capacity of 422.6 mA h/g. We ascribe the enhanced lithium storage performances to the novel hierarchical architectures achieved from the rational design.

A series of new tetrathiafulvalenes, with double alkylthiol or alkyldisulfide substitution, have been prepared with a synthetic procedure that allows variation of different substituents. The target compounds 6a-e and 15e-i are sparsely soluble in organic solvents, but TTFs 6d and 15g gave a relatively dense packed monolayer upon exposure to gold surfaces.

The aviation industry relies on lightweight carbon fiber-reinforced polymers (CFRP) for fuel efficiency, which necessitates lightning strike protection (LSP) and electromagnetic shielding due to their electrical insulating characteristics. Traditional metallic meshes used for LSP are heavy and corrosion-prone, prompting the exploration of alternatives. This research showcases CFRP nanocomposites with enhanced LSP properties through the incorporation of graphene nanoplatelets (GNPs) and carbon nanotubes (CNTs). While the enhanced conductivity in the nanofilled epoxy matrix did not impact the overall conductivity of CFRP panels, a significant damage reduction was observed after simulated lightning strike tests. Similar approaches in the literature have also noted this discrepancy, but no attempts to reconcile it have been made. This work provides a framework to explain the damage reduction mechanism while accounting for the modest conductivity improvements in the nanoreinforced CFRPs. Additionally, a simple, nondestructive method to assess surface resin degradation after a lightning strike test is proposed, based on the fluorescence of diphenyl ketones. The discussion is supported by electrical conductivity measurements, damage pattern evaluation using the proposed UV-illumination method, ATR-FTIR, and scanning electron microscopy analysis pre- and postlightning strike simulation.

As one of the major causes of antimicrobial resistance, beta-lactamase develops rapidly among bacteria. Detection of beta-lactamase in an efficient and low-cost point-of-care testing (POCT) way is urgently needed. However, due to the volatile environmental factors, the quantitative measurement of current POCT is often inaccurate. Herein, we demonstrate an artificial intelligence (AI)-assisted mobile health system that consists of a paper-based beta-lactamase fluorogenic probe analytical device and a smartphone-based AI cloud. An ultrafast broad-spectrum fluorogenic probe (B1) that could respond to beta-lactamase within 20 s was first synthesized, and the detection limit was determined to be 0.13 nmol/L. Meanwhile, a three-dimensional microfluidic paper-based analytical device was fabricated for integration of B1. Also, a smartphone-based AI cloud was developed to correct errors automatically and output results intelligently. This smart system could calibrate the temperature and pH in the beta-lactamase level detection in complex samples and mice infected with various bacteria, which shows the problem-solving ability in interdisciplinary research, and demonstrates potential clinical benefits.

Melem is the basic structural unit of g-C3N4. When directly utilized as a photocatalyst, the separation efficiency of photogenerated electron-hole pairs is low. In this study, we constructed a Melem-based all-organic heterojunction (PICN) by reacting the -NH2 at the terminal of the Melem unit with the anhydride of PDA. The photocatalytic efficiency for H2O2 production of the heterojunction is 4.2 times that of CN. Introducing -Cl at the bay position of PDI further enhances the photocatalytic H2O2 production efficiency by 1.6 times. This enhancement is attributed to the introduction of -Cl, which not only broadens the UV-visible light absorption range of the sample but also improves the interface electron transfer efficiency between Melem and PDICl. Moreover, the introduction of -Cl can also reduce the overpotential of the O-2 reduction reaction on the surface of the sample. These novel findings may provide insights for the design of organic heterojunction photocatalysts.

Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd₂O₃ nanocrystals.

Materials and methods: Gd₂O₃ nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd₂O₃ was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI).

Results: Results showed a considerable relaxivity increase for the Gd₂O₃–DEG particles compared to Gd-DTPA. Both T ₁ and T ₂ relaxivities in the presence of Gd₂O₃–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T₁-weighted spin echo sequence.

Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd₂O₃–DEG nanocrystals as contrast agent. The high T ₁ relaxation rate at low concentrations of Gd₂O₃ nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.

Two-dimensional materials offer a unique platform for sensing where extremely high sensitivity is a priority, since even minimal chemical interaction causes noticeable changes inelectrical conductivity, which can be used for the sensor readout. However, the sensitivity has to becomplemented with selectivity, and, for many applications, improved response- and recovery times are needed. This has been addressed, for example, by combining graphene (for sensitivity) with metal/oxides (for selectivity) nanoparticles (NP). On the other hand, functionalization or modification of the graphene often results in poor reproducibility. In this study, we investigate thegas sensing performance of epitaxial graphene on SiC (EG/SiC) decorated with nanostructured metallic layers as well as metal-oxide nanoparticles deposited using scalable thin-film depositiontechniques, like hollow-cathode pulsed plasma sputtering. Under the right modification conditions the electronic properties of the surface remain those of graphene, while the surface chemistry can betuned to improve sensitivity, selectivity and speed of response to several gases relevant for airquality monitoring and control, such as nitrogen dioxide, benzene, and formaldehyde.

The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue-and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3-5 nm in size, have r(1)-relaxivities between 7-13 mM(-1) s(-1) and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

Gadolinium chelates are employed worldwide today as clinical contrast agents for magnetic resonance imaging. Until now, the commonly used linear contrast agents based on the rare-earth element gadolinium have been considered safe and well-tolerated. Recently, concerns regarding this type of contrast agent have been reported, which is why there is an urgent need to develop the next generation of stable contrast agents with enhanced spin-lattice relaxation, as measured by improved T-1 relaxivity at lower doses. Here, we show that by the integration of gadolinium ions in cerium oxide nanoparticles, a stable crystalline 5 nm sized nanoparticulate system with a homogeneous gadolinium ion distribution is obtained. These cerium oxide nanoparticles with entrapped gadolinium deliver strong T-1 relaxivity per gadolinium ion (T-1 relaxivity, r(1) = 12.0 mM(-1) s(-1)) with the potential to act as scavengers of reactive oxygen species (ROS). The presence of Ce3+ sites and oxygen vacancies at the surface plays a critical role in providing the antioxidant properties. The characterization of radial distribution of Ce3+ and Ce4+ oxidation states indicated a higher concentration of Ce3+ at the nanoparticle surfaces. Additionally, we investigated the ROS-scavenging capabilities of pure gadolinium-containing cerium oxide nanoparticles by bioluminescent imaging in vivo, where inhibitory effects on ROS activity are shown.

The transition to green and sustainable catalysts necessitates efficient and safe preparation techniques using abundant and renewable resources. Many metal nanoparticles (NPs) are excellent catalysts but suffer from poor colloidal stability. NP immobilization or fabrication of metal nanostructures on solid supports can avoid issues with NP aggregation and facilitate the reuse of catalysts, but it may result in a decrease in the catalytic performance of the NPs. Here, we show that well-defined colloidal silver, gold, and platinum NPs can be self-assembled in bacterial nanocellulose (BC) membranes, yielding BC-NP nanocomposites that are highly catalytically active using the reduction of 4-nitrophenol (4-NP) as a model reaction. The large effective surface area of BC enables the assembly of large quantities of NPs, resulting in materials with excellent catalytic performance. To address the mass transport limitations of reactants through the 3D nanofibrillar BC network, the membranes were dissociated using sonication to produce dispersed nanocellulose fibrils. This process dramatically reduced the time required for the adsorption of the NPs from days to minutes. Moreover, the catalytic performance of the nanofibril-supported NPs was drastically improved. A turnover frequency above 21,000 h(-1) was demonstrated, which is more than one order of magnitude higher than that for previously reported soft substrate-supported AuNP-based catalytic materials. The ease of fabrication, abundance, and low environmental footprint of the support material, along with reusability, stability, and unprecedented catalytic performance, make BC-NP nanocomposites a compelling option for green and sustainable catalysis.

The size distribution and magnetic properties of ultra-small gadolinium oxide crystals (US-Gd₂O₃) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r₁, r₂) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd₂O₃ nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol (DEG)-capped US-Gd₂O₃ nanocrystals were reacted with PEG-silane (MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd³⁺ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering (DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG–Gd₂O₃ and PEG-silane–SPGO (Gd₂O₃,< 40 nm diameter). The small and narrow size distribution of US-Gd₂O₃ was confirmed with TEM (~3 nm) and DLS. PEG-silane–US-Gd₂O₃ relaxation parameters were twice as high as for Gd–DTPA and the r₂/r₁ ratio was 1.4. PEG-silane–SPGO gave low r₁ relaxivities and high r₂/r₁ ratios, less compatible with positive contrast agent requirements. Higher r₁ were obtained with PEG-silane in comparison to DEG–Gd₂O₃. Treatment of DEG–US-Gd₂O₃ with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG-covered Gd₂O₃ nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.

Intracellular viscosity plays an important role in regulating cellular morphology and physiology and is closely related to a host of diseases. Especially, the changes in mitochondrial viscosity will cause some common diseases such as hyperlipidemia, Alzheimer's disease and cancer. In this work, we report the design of a red-emissive molecular rotor for the detection of mitochondrial viscosity in live cells. The probe showed fascinating performance, such as specific targeting to mitochondria, high sensitivity to viscosity, and rapid fluorescence response, especially the dual response mode of fluorescence intensity and fluorescence lifetime. By using this probe, we realized monitoring of the mitochondrial viscosity variations in live cells under different physiological processes. Our study offers an opportunity to discover potential tools for mitochondria-related physiology and pathology investigation. A D-pi-A typed fluorescence lifetime probe for sensitively detecting viscosity has been designed and synthesized. BSOH has been successfully applied to real-time monitoring mitochondrial viscosity in live cells by fluorescence lifetime imaging.

The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)2O3 (0 e x e 1) were prepared by the combustion method and thoroughly characterized (by X-ray di.raction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and there has been a huge development in the fields of molecular imaging and intracellular markers.

Previous studies have shown that gadolinium oxide (Gd₂O₃ ) nanoparticles generate higher relaxivity than currently available Gd chelates. The Gd₂O₃ nanoparticles are also promising for MRI cell tracking. The aim of the present work was to study cell labeling with Gd₂O₃ nanoparticles and to improve techniques for monitoring hematopoietic stem cell migration by MRI.

We studied particle uptake in two cell lines; the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd₂O₃ nanoparticles as well as superparamagnetic iron oxide particles (SPIOs) for comparison. In addition, it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by microscopic techniques, MRI and analyzed for particle content.

Results showed that particles were intracellular, however in Ba/F3 only sparsely. The relaxation times were shortened with increasing particle concentration. Overall relaxivities, r₁ and r₂ for Gd₂O₃ nanoparticles in all cell samples measured were 5.1 ± 0.3 and 14.9 ± 0.7 (s^-1mM^-1) respectively. Goodness of fit was 0.97 in both cases. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells.

Viability of treated cells was not significantly decreased and thus, we conclude that the use of Gd₂O₃ nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells.

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd₂O₃) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd₂O₃ nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd₂O₃ nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd₂O₃ nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r₁ and r₂ at 1.5 T and 21°C, for Gd₂O₃ nanoparticles in different cell samples were 3.6–5.3 s^-1 mM^-1 and 9.6–17.2 s^-1 mM^-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd₂O₃ nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd₂O₃ nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.

A new colorimetric and fluorogenic probe (RN3) based on rhodamine-B has been successfully designed and synthesized. It displays a selective response to Hg2+ in the aqueous buffer solution over the other competing metals. Upon addition of Hg2+, the solution of RN3 exhibits a naked eye observable color change from colorless to red and an intensive fluorescence with about 105-fold enhancement. The changes in the color and fluorescence are ascribed to the ring-opening of spirolactam in rhodamine fluorophore, which is induced by a binding of the constructed receptor to Hg2+ with the association and dissociation constants of 0.22 x 10(5) M-1 and 25.2 mM, respectively. The Jobs plot experiment determines a 1: 1 binding stoichiometry between RN3 and Hg2+. The resultant "turn-on" fluorescence in buffer solution, allows the application of a method to determine Hg2+ levels in the range of 4.0-15.0 mu M, with the limit of detection (LOD) calculated at 60.7 nM (3 sigma/slope). In addition, the fluorescence turn-off and color fading-out happen to the mixture of RN3-Hg2+ by further addition of I- or S2-. The reversible switching cycles of fluorescence intensity upon alternate additions of Hg2+ and S2- demonstrate that RN3 can perform as an INHIBIT logic gate. Furthermore, the potential of RN3 as a fluorescent probe has been demonstrated for cellular imaging. (C) 2016 Elsevier B.V. All rights reserved.

A new visible light excitable fluorescent probe (1) is synthesized by appending a hydroxymethyl-pyridine to rhodamine B hydrazide. The probe displays very specific Hg2+-induced colour change and fluorescent enhancement in the aqueous systems. The "turn-on" response of fluorescence is based on a binding-induced ring-opening process from the spirolactam (nonfluorescent) to acyclic xanthene (fluorescent) in rhodamine B. The coordinating atoms O-center dot-N-N-O-center dot from the hydroxymethyl-pyridine and rhodamine B hydrazide play dominant role in the formation of a complex with 1:1 stoichiometry of Hg2+ to 1. It exhibits a linear response in the range of 0.1-5 mu M with the limit of detection (LOD) of 15.7 nM (3 sigma/slope), while the calculated value of the association constant of Hg2+/1 is 0.70 x 10(5) M-1. Furthermore, confocal microscopy imaging experiment demonstrates the probe 1 can be applied as a fluorescent probe for visualization of Hg2+ in living HeLa cells.

We design and synthesize a new ratiometric fluorescent chemodosimeter (S1) for the selective and sensitive detection of Hg2+. Upon addition of Hg2+, the emission of the S1 exhibits a large bathochromic shift from 393 to 515 nm (up to 122 nm) which is ascribed to an intramolecular charge transfer process in the resultant. The Hg2+-induced dethioacetalization for sensing mechanism has been demonstrated by using high-performance liquid chromatography analysis of the sensing process. The interference experiments further demonstrate that S1 exhibits very high selectivity towards Hg2+ over other coexisting cations/anions. Subsequently, a good linearity of the concentrations of Hg2+ (0-15 mu M) vs the ratiometric signals (I-515/I-393) allows a fluorogenic method for the quantitative detection of Hg2+, with the limitation of detection determined to be 5.22 x 10(-7) M. (C) 2016 Elsevier B.V. All rights reserved.

By ingeniously using a (imino)coumarin-precursor, three reactive fluorogenic probes of MP, FP, and FMP have been fabricated in a single facile synthetic route. MP and FP are able to respectively act as selective "turn-on" fluorescent probes for detecting Hg2+ and F- in buffer solution via specific analyte-induced reactions. Linear ranges for the detection of Hg2+ and F- are 0-10 mu M and 0-100 mu M with the limits of detection (LODs) of 4.0 x 10(-8) M and 1.14 x 10(-6) M (3 delta/slope), respectively. FMP is able to work as a molecular "AND" logic gate-based fluorogenic probe for monitoring the coexistence of Hg2+ and F- via a multistep reaction cascade. The analytes-induced sensing mechanisms have been determined by using high-performance liquid chromatography analysis (HPLC). In addition, three probes show negligible toxicity under the experimental conditions, and are successfully used for monitoring Hg2+ and F- in living cells with good cell permeability. The success of the work demonstrates that ingenious utility of specific analyte-induced reactions and conventional concepts on the appropriate molecular scaffold can definitely deliver tailor-made probes for various intended sensing purposes. (C) 2018 Published by Elsevier B.V.

In this work, we report a novel protein-based nanoprobe (PNP) that can be employed for quantitative analysis of Cu2+ in pure water medium and real samples. Structurally, the proposed nanoprobe comprises a biofriendly protein (hen egg-white lysozyme (HEWL)) and a Cu2+-specific chromogenic agent, where HEWL acts as a nanocarrier encapsulating a structurally tailored rhodamine B derivate. The resulting PNP exhibits a hydrodynamic diameter of similar to 106 nm and efficiently disperses in water, enabling the detection of Cu2+ in pure aqueous systems without the aid of any organic co-solvents. The high sensitivity and selectivity of PNP allow the colorimetric detection of Cu2+ in the presence of other metal interferents with a low detection limit of 160 nM. The satisfying recovery of trace level Cu2+ in environmental samples demonstrate the great potential of employing PNP for the determination of Cu2+ in actual applications. Most importantly, the simple co-grinding method employing proteins and chromogenic agents provides a novel strategy to generate sensing systems that are useful detection of pollutants in aqueous samples. (C) 2021 Elsevier B.V. All rights reserved.

A rhodamine B-based sensor (RS) was designed and synthesized by a combination of the spirolacton rhodamine B (fluorophore) and multidentate chelates (ionophore) with high affinity towards Hg2+. In the presence of Hg2+, the resulting red-orange fluorescence (under UV light) and naked eye red color of IDS are supposed to be used for quantitative and qualitative measurement of Hg2+. Further fluorescent titration and analysis demonstrate that RS can selectively detect Hg2+ within 1 s with a low limit of detection (LOD) of 16 nM in acetonitrile media, meanwhile, the association constant (K-a) was calculated to be 0.32 x 10(5) M-1. More importantly, the resultant complex (RSHg) of RS and Hg2+ has also been successfully applied to detect limited water content in acetonitrile solution. (C) 2020 Published by Elsevier B.V.

Hypochlorous acid (HClO) is one of the most important ROS (reactive oxygen species) and common pollutant in tap-water. However, the determination of HClO with fast response and high sensitivity/selectivity is still an urgent demanding. Here we fabricated a ratiometric fluorescent probe RC based on TBET (through-bond energy transfer) on the platform of coumarin and rhodamine with the thiosemicarbazide group as the linker. This probe could display the characteristic fluorescence emission of coumarin. Upon addition of HClO, the linker was reacted into an oxadiazole, resulting in the opening of spiro-ring of rhodamine. The resultant then gives ratiometric fluorogenic changes. The probe exhibits fast response and high selectivity and sensitivity towards HClO with a low limit of detection (similar to 140 nM). Eventually, RC is successfully applicated for determining spiked HClO in water samples and imaging endogenous HClO in living cells. (C) 2019 Published by Elsevier B.V.

Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained Eu-III-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r(1)=6.4 and 6.3s(-1)mM(-1) with r(2)/r(1) ratios close to unity at 1.4T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.

A facile one-step Cu(I)-catalyzed "click" reaction, between a dansyl-azide and a propargyl-substituted rhodamine B hydrazide, is employed to fabricate a novel FRET ratiometric "off-on" fluorescent probe. The sensitive emission of the donor, a dansyl group, overlaps perfectly with the absorption of the acceptor, xanthene in the open-ring rhodamine. The proposed probe shows high selectivity towards Cu2+. The ratio of emission intensities at 568 and 540 nm (I-568/I-540) exhibits a drastic 28-fold enhancement upon addition of Cu2+. The probe shows an excellent linear relationship between emission ratios and the concentrations of Cu2+ from 10 to 50 mu M, with a detection limit (S/N = 3) of 0.12 mu M. The preliminary cellular studies demonstrated that the probe is cell membrane permeable and could be applied for ratiometric fluorescence imaging of intracellular Cu2+ with almost no cytotoxicity. The ingenuity of the probe design is to construct a FRET donor-acceptor interconnector and a selective receptor simultaneously by "click" reaction. The strategy was verified to have great potential for developing novel FRET probes for Cu2+.

We strategize to utilize the precursors of (imino) coumarin fluorophores to deliver novel reactive Cu+ probes, where tris[(2-pyridyl)-methyl] amine (TPA) works as a reactive receptor towards Cu+. To verify this strategy, CP1, a representative probe and relevant sensing behaviors towards Cu+ are presented here. CP1 features good solubility and fast response for monitoring labile copper in aqueous solution and live cells. The sensing mechanism of CP1 is determined by HPLC titration and mass spectrometric analysis. The probe CP1 exhibits a 60-fold fluorescence enhancement and a detection limitation of 10.8 nM upon the detection of Cu+. CP1 is further applied for imaging labile copper in live cells. This work provides a starting point for future development of Cu+ probes, based on in situ formation of (imino) coumarin scaffolds, as well as their further investigations of copper signaling and biological events. (C) 2016 Elsevier B.V. All rights reserved.

Reactive oxygen species (ROS) regulating the release of free zinc ions (Zn2+) in cellular lysosome is closely related to various pathways of cellular signal transduction, such as inflammation and oxidative stress. Directly visualizing Zn2+ release in lysosome is essential for in-depth understanding these physiological processes, and is still an atelic challenge. In this work, we successfully fabricate a lysosome-specific Zn2+ fluorescent probe and achieve the visualization of ROS-induced Zn2+ release in lysosome of inflammatory cells. The as-prepared probe combines a green fluorophore, an ionophore with five-dentate sites, and a morpholine as the lysosome-specific localization moiety. The fluorescence of the fluorophore in the free probe is suppressed by a photoinduced electron transfer (PET) process from nitrogen atoms in the ionophore. Upon the addition of Zn2+, the fluorescence can be promoted immediately, achieving the real-time detection. Meanwhile, the probe is sensitive and selective to Zn2+, which provides the capability to detect low-concentration of free Zn2+ in lysosomes. Accordingly, the Zn2+ release was clearly observed in lysosome with the increase of ROS levels when the inflammation occurred in living cells. (c) 2018 Published by Elsevier B.V.

Mixed transition metal oxides (MTMOs) are deemed as promising anode materials for lithium-ion batteries (LIBs) because of the high theoretical capacity and low cost. However, the low electrical conductivity, agglomeration effects, and huge volume variation during discharging/charging still seriously restrict the actual applications of MTMOs as anode materials. Herein, a novel core-shell structure of CoSnO3@carbon-caged NiCo2O4 nanobox (CNC) is rationally designed. It starts from the preparation of CoSnO3@ZIF-67 core-shell nanocubes, followed by chemical etching/anion exchange, dopamine coating and carbonization at high temperature in sequence. It is shown that the CNC achieves high activities from the applied MTMOs components, excellent relief of volume variation from the unique double hollow structure, improved conductivity and inhabited aggregations from the uniform-coated outmost carbon shell, and effective ion/electron transfer rates from the synergetic effects. As a result, the CNC exhibits a discharge capacity of 1548 mA h g(-1) at the first cycle and a retention capacity of 992 mA h g(-1) after 100 cycles at 0.1 A g(-1). In addition, it exhibits a high reversible capacity of about 670 mA h g(-1) after 500 cycles at a current density of 1 A g(-1). The improved Li+ storage performances of CNC demonstrates that such rational design of double hollow structure could be a novel strategy to apply MTMOs as anode materials of LIBs.

Photo-/electrocatalysis serves as a cornerstone in addressing global energy shortages and environmental pollution, where the development of efficient and stable catalysts is essential yet challenging. Despite extensive efforts, it's still a formidable task to develop catalysts with excellent catalytic behaviours, stability, and low cost. Because of its high precision, favorable controllability and repeatability, radiation technology has emerged as a potent and versatile strategy for the synthesis and modification of nanomaterials. Through meticulous control of irradiation parameters, including energy, fluence and ion species, various inorganic photo-/electrocatalysts can be effectively synthesized with tailored properties. It also enables the efficient adjustment of physicochemical characteristics, such as heteroatom-doping, defect generation, heterostructure construction, micro/nanostructure control, and so on, all of which are beneficial for lowering reaction energy barriers and enhancing energy conversion efficiency. This review comprehensively outlines the principles governing radiation effects on inorganic catalysts, followed by an in-depth discussion of recent advancements in irradiation-enhanced catalysts for various photo-/electrocatalytic applications, such as hydrogen and oxygen evolution reactions, oxygen reduction reactions, and photocatalytic applications. Furthermore, the challenges associated with ionizing and non-ionizing radiation are discussed and potential avenues for future development are outlined. By summarizing and articulating these innovative strategies, we aim to inspire further development of sustainable energy and environmental solutions to drive a greener future.

Magnetic Fe3O4@ZnO@nitrogen-doped carbon (Fe3O4@ZnO@N-C) composites with multiple core-shell structures have been successfully synthesized by calcination of ZIF-8 coated Fe3O4@ZnO core-shell nanocrystals. The morphologies and microstructural characteristics are investigated by X-ray diffraction, Fourier-transform infrared spectrometer, transmission electron microscopy, X-ray photoelectron spectroscopy, physical adsorption of nitrogen, and UV-vis diffuse reflectance spectroscopy. The photocatalytic performances are tested by degrading methylene blue (MB) in aqueous solutions under the irradiation of imitative sunlight. The photocatalytic trials indicate that the Fe3O4@ZnO@N-C composites exhibit improved degradation efficiency compared to the Fe3O4@ZnO precursor. The photocatalytic efficiencies of the as-prepared Fe3O4@ZnO@N-C composites towards MB are 93% under irradiation of imitative sunlight for 90 min and still maintained to be 87% after 6 recycles, which shows very good stability and recyclability. Nitrogen-doped carbon is believed to extend the absorption spectra to the visible-light region. The photodegradation kinetics via using the as-prepared Fe3O4@ZnO@N-C composite as a novel photocatalyst are systematically investigated. (C) 2019 Elsevier Ltd. All rights reserved.

A very large surface to volume ratio of nanoporous silicon (PS) produces a high density of surface states, which are responsible for uncontrolled oxidation of the PS surface. Hence it disturbs the stability of the material and also creates difficulties in the formation of a reliable electrical contact. To passivate the surface states of the nanoporous silicon, noble metals (Pd, Ru, and Pt) were dispersed on the PS surface by an electroless chemical method. GIXRD (glancing incidence X-ray diffraction) proved the crystallinity of PS and the presence of noble metals on its surface. While FESEM (field emission scanning electron microscopy) showed the morphology, the EDX (energy dispersive X-ray) line scans and digital X-ray image mapping indicated the formation of the noble metal islands on the PS surface. Dynamic SIMS (secondary ion mass spectroscopy) further confirmed the presence of noble metals and other impurities near the surface of the modified PS. The variation of the surface roughness after the noble metal modification was exhibited by AFM (atomic force microscopy). The formation of a thin oxide layer on the modified PS surface was verified by XPS (X-ray photoelectron spectroscopy).

Nano porous silicon (PS) was formed on p-type monocrystalline silicon of 2-5 Omega cm resistivity and (100) orientation by electrochemical anodization method using HF and ethanol as the electrolytes. High density of surface states, arising due to its nano structure, is responsible for the uncontrolled oxidation in air and for the deterioration of the PS surface with time. To stabilize the material PS surface was modified by a simple and low cost chemical method using PdCl2 solution at room temperature. X-ray photoelectron spectroscopy (XPS) was performed to reveal the chemical composition and the relative concentration of palladium on the nanoporous silicon thin films. An increase of SiO2 formation was observed after PdCl2 treatment and presence of palladium was also detected on the modified surface. I-V characteristics of Al/PS junction were studied using two lateral Al contacts and a linear relationship was obtained for Pd modified PS surface. Stability of the contact was studied for a time period of around 30 days and no significant ageing effect could be observed.

Over the years a number of epidemiological studies have shown that PM from combustion sources such as motor vehicles contributes to respiratory and cardiovascular morbidity and mortality.Especially so do the ultra-fine particles (UFPs) with a diameter less than 0.1 micrometer.UFPs from combustion engines are capable to translocate over the alveolar–capillary barrier.  When nano-sized PM (nanoparticles, NP), which are small enough to enter the blood stream, do so they are likely to interact with plasma proteins and this protein-NP interaction will probably affect the fate of and the effects caused by the NPs in the human body. Here, by using a proteomic approach, we present results showing that several proteins indeed are associated to NPs that have in vitro been introduced to human blood plasma.

A complementary metal-oxide-semiconductor (CMOS) chip biosensor was developed for cell viability monitoring based on an array of capacitance sensors utilizing a ring oscillator. The chip was packaged in a low temperature co-fired ceramic (LTCC) module with a flip chip bonding technique. A microcontroller operates the chip, while the whole measurement system was controlled by PC. The developed biosensor was applied for measurement of the proliferation stage of adherent cells where the sensor response depends on the ratio between healthy, viable and multiplying cells, which adhere onto the chip surface, and necrotic or apoptotic cells, which detach from the chip surface. This change in cellular adhesion caused a change in the effective permittivity in the vicinity of the sensor element, which was sensed as a change in oscillation frequency of the ring oscillator. The sensor was tested with human lung epithelial cells (BEAS-2B) during cell addition, proliferation and migration, and finally detachment induced by trypsin protease treatment. The difference in sensor response with and without cells was measured as a frequency shift in the scale of 1.1 MHz from the base frequency of 57.2 MHz. Moreover, the number of cells in the sensor vicinity was directly proportional to the frequency shift.

There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd₂O₃) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd₂O₃-labeled cells have shorter T₁ and T₂ relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd₂O₃ nanoparticles can be used as a positive contrast agent for cell labeling. The r₁ for cell samples was 4.1 and 3.6 s^-1 mm^-1 for cell culture medium. The r₂ was 17.4 and 12.9 s^-1 mm^-1, respectively. For r₁, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (p_r1 = 0.36), but r₂ was significantly different for the two different series (p_r2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd₂O₃ nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.

Accurate models for the human diploe have to take into account any structural differences in the four main areas of the calvaria bones. In this study the technique of X-ray computed microtomography (mu-CT) along with image analysis was used in order to visualize and quantitatively analyze differences in the micro-architecture of the human calvarium diploe. A bone specimen from each area of the skull (temporal, frontal, parietal and occipital) was extracted from a human donor and each specimen was characterized in terms of density, specific surface area, trabecular thickness and anisotropy. The obtained results reveal that in the considered case there are structural differences which therefore can be useful for refining traditional models that assume equal conditions throughout the skull.